Novel Adenoid Cystic Carcinoma Drug Earns FDA Breakthrough Therapy Status

The FDA has granted breakthrough therapy designation to emiltatug ledadotin (Emi-Le) as a treatment for patients with adenoid cystic carcinoma (ACC), according to a press release from the developer, Servier.¹ Specifically, the designation was granted for the management of locally advanced, recurrent, or metastatic ACC showing solid histology or high-grade transformation.

Developers designed Emi-Le as an anti–B7-H4 Dolasynthen antibody drug conjugate (ADC) with an optimized drug-to-antibody ratio of 6 and an auristatin-F HPA payload demonstrating a controlled bystander effect. According to the press release, the agent has previously received fast track designation for the treatment of adults with advanced or metastatic triple-negative breast cancer and those with advanced or metastatic HER2-low or HER2-negative breast cancer following previous topo-1 ADCs.

ACC is a rare malignancy that develops in the secretory glands—usually in the head and neck—and in other parts of the body. More than 200,000 patients have been diagnosed with ACC across the world. The press release noted that there are no currently approved or preferred systemic therapy options for patients with advanced or metastatic ACC. Although most patients receive surgery or radiation, disease recurrence occurs in 50% of cases.

“At Servier, we are committed to pursuing first‑in‑class medicines for rare diseases in oncology. This breakthrough therapy designation for Emi‑Le will help accelerate development and may provide an important new treatment option for patients with few effective choices today,” Peter Adamson, global head of Oncology Clinical Development at Servier, stated in the press release.¹

Investigators are currently assessing the safety, tolerability, and anti-tumor activity of Emi-Le among patients with different solid tumors as part of a multicenter phase 1 trial (NCT05377996). The trial population includes those with aggressive ACC, breast cancer, endometrial cancer, and ovarian cancer.

The multicenter trial was opened in 2022.² According to preliminary clinical data reported in phase 1, Emi-Le appeared to be well tolerated and produced confirmed objective responses across different types of tumors.

In the single-arm study, patients received Emi-Le monotherapy via intravenous administration.³ The trial’s primary end points included the frequency of adverse effects (AEs) considered to be dose-limiting toxicities and related to treatment with Emi-Le during the dose-escalation portion, incidence of AEs during the dose-escalation and dose-expansion portions, and objective response rate during the dose-expansion portion. Secondary end points included duration of response, pharmacokinetics, and antidrug antibodies and neutralizing antibodies.

Patients 18 years and older with recurrent or advanced solid tumors, an ECOG performance status of 0 or 1, and tumor tissues available from an archive or fresh tumor biopsy were eligible for enrollment on the trial. Patients with triple-negative breast cancer or a history of brain metastases or with neurologic symptoms suspicious for brain metastases were required to have a brain MRI during the screening period unless obtained within 30 days before screening.

Those with prior treatment with an ADC harboring an auristatin payload, major surgery within 28 days of beginning study treatment, or a diagnosis of an additional malignancy requiring active therapy were ineligible for enrollment on the trial. Patients were also unable to enroll if they had untreated central nervous system metastases; prior B7-H4–targeted therapy; a history of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver diseases; or clinically significant cardiovascular disease. Having current severe, uncontrolled systemic disease or intercurrent illness that may have interfered with per-protocol assessments was additional grounds for exclusion from the trial.

References

1. Emiltatug ledadotin (Emi-Le) granted breakthrough therapy designation by the U.S. FDA for adenoid cystic carcinoma (ACC). News release. Servier. May 12, 2026. Accessed May 13, 2026. https://tinyurl.com/srs8wfev
2. Emi-Le. Day One Biopharmaceuticals. Accessed May 13, 2026. https://tinyurl.com/22vxpkat
3. A study of XMT-1660 in participants with solid tumors. ClinicalTrials.gov. Updated April 14, 2026. Accessed May 13, 2026. https://tinyurl.com/5n7a25p8